tbuckley/cabot-search huggingface dataset:
Antibody to Epstein-Barr Virus in American Patients With Carcinoma of the Nasopharynx
Authors: John M. Goldman
Journal: JAMA (1971)

Serum antibody to Epstein-Barr virus (EBV) was measured in 21 patients with nasopharyngeal carcinoma (NPC), in 3 patients with lymphoma in the nasopharynx, and in control groups. Fifteen of 21 (71.4%) of the NPC patients had high anti-EBV antibody titers ([unk]1:160), whereas only six of 140 (4.3%) had such titers in the combined control groups; the geometric mean titer (GMT) of the NPC patients was 1:239, compared with a GMT in the lymphoma patients of 1:20 and a GMT in the control groups of 1:29. The NPC patients were categorized by the histologic type of their tumors, but no relationship between tumor histologic type and antibody titer was discernible. The data support the concepts that EBV appears to be specifically associated with NPC (as well as with Burkitt's lymphoma and infectious mononucleosis) and that such a relationship may well be causal.
The Structure and Meaning of Psychoanalysis as Related to Personality and Behavior.
Journal: JAMA (1931)

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Endoscopy International Open – recently published
Journal: Endoscopy (2015)

See also: A novel colonoscope with panoramic visualization detected more simulated polyps than conventional colonoscopy in a live swine modelEndosc Int Open 2015; 03(06): E642-E645DOI: 10.1055/s-0034-1393080 See also: Is virtual chromoendoscopy useful in the evaluation of subtle ulcerative small-bowel lesions detected by video capsule endoscopy?Endosc Int Open 2015; 03(06): E615-E620DOI: 10.1055/s-0034-1393063 See also: Morphometric study of the blood supply of pedunculated colon polyps: What is the optimal position on the stalk for snare resection?Endosc Int Open 2015; 03(06): E655-E658DOI: 10.1055/s-0034-1393082
Lung Cancer in Turkey
Authors: Ayten Kayı Cangır, Perran Fulden Yumuk, Serpil Dizbay Sak, Serap Akyürek, Yeşim Eralp, Ülkü Yılmaz, Uğur Selek, Atilla Eroğlu, Ali Murat Tatlı, Fazilet Öner Dinçbaş, Saadettin Kılıçkap, Mehmet Ali Nahit Şendur, Asli Görek Dilektaşlı, Hakan Şat Bozcuk, Serdar Özkök, İlhan Öztop, Erkan Topkan, Şükrü Dilege, Akın Kaya, Ahmet Demirkazık
Journal: Journal of Thoracic Oncology (2022)
And Still They Come Over Troubled Waters: Can Asia’s Third-Generation EGFR Tyrosine Kinase Inhibitors (Furmonertinib, Aumolertinib, Rezivertinib, Limertinib, Befotertinib, SH-1028, and Lazertinib) Affect Global Treatment of EGFR+ NSCLC
Authors: Sally C.M. Lau, Sai-Hong Ignatius Ou
Journal: Journal of Thoracic Oncology (2022)
Surgery on a Primary Cranial Vault Lymphoma
Authors: Pablo de la Fuente, Kapil Rajwani, Iñigo Sistiaga, Jose Pedro Lavrador
Journal: Neuro-Oncology (2022)

Abstract AIMS Unique cranial involvement in Lymphomas is extraordinary and when it occurs, it is usually accompanied by systemic involvement. The role of the surgery in these cases is still unclear. METHOD Case report of a 72-year-old female with a primary cranial vault lymphoma with primary surgical management at time of recurrence. RESULTS 72-year-old female, with a background of treated breast cancer and ischemic heart, presented with a right parieto-occipital lytic bone lesion with a soft tissue mass with a diagnosis of Non-Hodgkin’s Lymphoma Type B, compatible with follicular lymphoma, with no other symptoms Systemic involvement was ruled out in PET CT bone marrow biopsy. First-line chemotherapy was precluded due to the cardiotoxicity, and she was started on Rituximab-Bendamustine and radiotherapy. PET-CT one year later shows local progression with lytic destruction. The MRI showed an imprint on the brain and a lesion in intimate contact with the superior longitudinal sinus. As an apparently localized lesion and the patient could not receive the optimal chemotherapy treatment, a craniectomy was proposed. Fifteen months after surgery the patient is free of disease on PET CT. CONCLUSION Primary cranial lymphoma is an unusual entity which precludes clear algorithms. The primary treatment is the chemotherapy, nonetheless, If the patient cannot receive the optimal treatment due to his background or in the presence of recurrent disease with limited treatment options, surgery should be considered if technically plausible and adequate to patient’s performance status.
Impact of the Neuro-Radiologist and Neuro-Surgeon in Contouring With the Neuro-Oncologist on Local Relapse Rates for Brain Metastases Treated With Stereotactic Radiosurgery
Authors: Maxwell Robinson, Karen Sayal, Clare Tunstall, Sriram Padmanaban, Rhona Watson, Pieter Pretorious, Robin Joseph, Sanjeeva Jeyaretna, Claire Hobbs
Journal: Neuro-Oncology (2022)

Abstract AIMS The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS). METHOD Lesions were contoured first by clinical oncologist then reviewed/edited by MDT. Iinitial contour was compared with final using Jaccard conformity and geographical miss indices. Dosimetric impact of contouring change was assessed using plan metrics to both original and final contour. The impact of contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up. RESULTS 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32-1.00) and 38% needed significant editing (JCI&amp;lt;0.95). Mean GMI was 0.03 (0.0-0.65) and 17% showed significant miss (GMI&amp;gt;0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p&amp;lt;0.05). Dosimetric analysis indicated a strong association of conformity with PTV dose metrics. Greater association was seen in resection cavity, i.e. geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate of 0.89 (0.8-0.94) at 40 months. Radio-necrosis free rate 0.9 (0.83-0.95) at 40 months with median 17 months to developing radionecrosis for those that did. CONCLUSION MDT contour review adds significant value to SRS resulting in reduced local recurrence rates. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist - particularly for resection cavities.
Brain Tumour Lessons From Alzheimer’s Disease: Beta-Amyloid and SorLA Expression in Glioblastoma
Authors: Lydia Jones, Vicky Jones, Lisa Shaw, Izabela Stasik, Christopher Smith
Journal: Neuro-Oncology (2022)

Abstract AIMS Exploring how two proteins strongly associated with Alzheimer’s disease are expressed in glioma. Amyloid beta (Aβ) is a peptide cleaved from amyloid precursor protein (APP) that is shuttled around the cell by sorting-related receptor with A-type repeats (SorLA). Low expression of SorLA has been linked to increased risk of Alzheimer’s disease as APP processing shifts towards production of the plaque-forming Aβ42 rather than the more benign Aβ40. METHOD Expression of Aβ40, Aβ42 and SorLA was determined in immortalised cell lines (grade 4 glioblastoma U87MG, grade 2 astrocytoma 1321N1, foetal astrocytes SVGp12), glioblastoma patient-derived cells (PD301, PD304) and normal human astrocytes through western blotting or immunocytochemistry. RESULTS SorLA was present in all cells. Relative optical density was more than 60-fold higher for U87MG glioblastoma cells and approximately 10-fold higher for 1321N1 astrocytoma cells than SVGp12 cells. Similarly, SorLA had a significantly higher expression (p&amp;lt;0.01) in patient derived cells than normal human astrocytes. High expression of SorLA was accompanied by lower Aβ42 in patient derived cells compared to normal human astrocytes. Expression of Aβ40 was similar across patient derived cells and normal human astrocytes. CONCLUSION These data suggest that SorLA is retained in glioblastoma and remains functional to drive APP processing away from Aβ42 production. Future work will determine how high SorLA expression contributes to the increased motility and invasiveness seen in glioblastoma cells by transfecting siRNA to knock down SorLA.
An Audit of Serial Stereotactic Biopsies at the WCFT Between 2018-2021
Authors: Connor Gilder, Piyali Pal
Journal: Neuro-Oncology (2022)

Abstract AIMS (1) To assess how often serial stereotactic brain biopsies of gliomas perform at Walton Centre between 20018 and 2021 allow clinically requisite molecular results, within the expected turnaround times. (2)Assess reasons for delay or not obtaining molecular results. METHOD All data obtained from LIMS (TDHC) and electronic patient records (eP2) at the Walton Centre Foundation Trust, and analysed in MS Excel. High grade glioma cases explored in detail. RESULTS Of 61 cases included, 45 were gliomas. 37 (61%) were HGGs i.e. GBMs or AAs. All requested molecular data could be obtained on 74% GBMs and 40% of AAs. One Oligodendroglioma remained ungraded. All the 4 DMGs could be issued final histological diagnosis based on immunohistochemistry and required no extra molecular tests. All requested molecular data could be obtained in 71% of LGG cases. MGMT results were obtained in 89% of GBM cases. NGS results were obtained in 57% of GBM cases. The average turnaround time from date of biopsy to authorised report 13 – 97 days, with a mean of 26 days. CONCLUSION (1) The majority of GBM cases yielded all requested molecular results. (2) Sample size was a limiting factor in obtaining molecular results. (3) Turnaround times have been compounded by failed molecular tests, ultimately affecting patient waiting times in HGGs. (4) Histological grading by mitotic index is not possible on small biopsy fragments. (5) If viable tumour cells are present, immunohistochemical molecular markers have proved valuable.
The Usefulness of Pre-Operative Extra-Cranial Imaging in Radiologically Suspicious Glioblastoma Multiforme in the West of Scotland: and a Proposal of an Imaging Diagnostic Pathway
Authors: Simon Lammy, Rebecca McPartlin, Elsie Bridgman, Janet Bouttell, Jennifer Brown
Journal: Neuro-Oncology (2022)

Abstract AIMS Objective: a CT chest, abdomen and pelvis (CT CAP) is probably unnecessary if a glioblastoma multiforme (GBM) is detected on initial CT brain (CTB) prior to definitive MRI. We audited its frequency to develop a management pathway METHOD Methods: 12-month retrospective case series from 2018 of patients having an initial CTB suspicious for GBM. We dichotomised patients into two groups a) tissue proven and b) non-tissue proven, due to these representing distinct patient profiles. We quantified frequencies of plain and contrast CTBs, CT CAPs and extra-cranial malignancy. RESULTS Results: Group 1 (total n=84 [mean age 59 years]): 64% had a CT CAP. Plain CTB occurred in 24% and contrast CTB in 76%. Extra-cranial malignancy was 8% and 12%. Group 2 (total n=47 [mean age 73 years]): 85% had a CT CAP. Plain CTB occurred in 22% and contrast CTB in 78%. Extra-cranial malignancy was 33% and 23%. Negative CT CAPs in ~88% of CTBs in Group 1 and ~75% of CTBs in Group 2. CONCLUSION Conclusions: patients having a contrast CTB as their initial imaging modality, being suggestive of GBM, prior to definitive MRI, and managed surgically, having no history of extra-cranial malignancy, do not need a CT CAP unless MRI is non-diagnostic.
Identification of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients
Authors: Chiara Cilibrasi, Thomas Simon, Marian Vintu, Christos Tolias, Mark Samuels, Nektarios Mazarakis, Murat Eravci, Nicholas Stewart, Giles Critchley, Giorgios Giamas
Journal: Neuro-Oncology (2022)

Abstract AIMS Description of effective biomarkers present in biofluids could prove invaluable in GBM diagnosis. Extracellular vesicles (EVs) are essential to intercellular crosstalk in the tumour bulk and circulating EVs have been described as a potential reservoir of GBM biomarkers. Therefore, EV-based liquid biopsies have been suggested as a promising tool for GBM METHOD Ethical approval was obtained for a prospective study of healthy donors and consenting GBM patients at the University Hospitals Sussex (Brighton). To identify GBM specific proteins, small EVs (sEVs) were isolated from plasma samples using differential ultracentrifugation and validated through Nanoparticles tracking analysis, transmission electron microscopy and detection of known sEVs markers such as CD9, CD63, CD81 and HSP70. sEVs content was characterised through mass spectrometry and bioinformatic tools. RESULTS Our data indicate the presence of a GBM inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation including VWF, FCGBP, C3, PROS1, and SERPINA1. Bioinformatic analysis highlighted that all potential markers exclusively identified in patient samples had already been linked with either GBM diagnosis, prognosis or associated signalling, suggesting that sEVs protein cargo could mirror the landscape of the original tumour and that selective circulating sEV-derived proteins might be used as hallmarks for GBM patients. CONCLUSION this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GBM diagnosis and, consequently, patients’ prognosis and quality of life.
Health-Related Quality of Life in Patients With High-Grade Glioma: A Systematic Review
Authors: Elen Sanpher, Layla Mitchell, Sumirat Keshwara, Abdurrahman Islim, Michael Jenkinson, Christopher Millward
Journal: Neuro-Oncology (2022)

Abstract AIMS Several studies have evaluated health-related quality of life (HRQoL) through patient-reported outcomes (PROs) in high-grade glioma (HGG) patients. No systematic review has summarised this increasingly important research area. METHOD Seven electronic databases were systematically searched. Primary research articles evaluating HRQoL in HGG patients through PRO assessment were included. Global, physical, mental, and social health were summarised descriptively. Risk of bias (RoB) of included studies was assessed using The Joanna Briggs Institute Critical Appraisal tool or Newcastle Ottawa Scale. Quality of study reporting was assessed using a modified ISOQOL checklist. RESULTS Twenty-six studies were included (4,451 patients): cross-sectional (n=14), longitudinal (n=12). RoB and quality of reporting were satisfactory. Ten PRO measurement instruments were identified, of which EORTC-QLQ-C30 (n=15) was utilised most frequently. Fatigue significantly impacted both physical and global health. HRQoL improved after surgery but recurrence, fatigue, and difficulties with activities of daily living were associated with worsening HRQoL. HGG patients had higher anxiety and depression scores than the general population, negatively impacting overall HRQoL. Social health was superior for patients with good supportive networks, but a majority do not return to full-time employment post-diagnosis. Long-term survivors reported improvements in their physical, social and emotional functioning over time. CONCLUSION With HGG life expectancy less than 12 months post-diagnosis, HRQoL is of paramount importance to patients. PRO assessment of HRQoL can be used to evaluate self-reported functioning and well-being in both routine practice and clinical trial settings and provide opportunities for timely intervention.
Improving the Odds - Long Term Survivors of Glioblastoma Multiforme (GBM)
Authors: Palwasha Khan Akbar, Hannah Lord
Journal: Neuro-Oncology (2022)

Abstract AIMS To review the data of patients in NHS Tayside who survived &amp;gt;24 months from a diagnosis of GBM, identifying trends in: (i) fixed demographic features; (ii) genetic mutations; (iii) treatment pathways. METHOD A retrospective case note review of patients with a new diagnosis of GBM 2015-2020, identifying those with &amp;gt;2 year survival. Data analysed: demographics (gender, age), mutations (IDH1, MGMT), and treatment (surgical, chemotherapy/radiotherapy). RESULTS 84 patients identified. 18 survived &amp;gt;24 months (2 year survival rate of 21.4%). Median survival = 31 months (range 24-110 months); 18 patients: M:F ratio = 1.6:1; Median age at diagnosis 54.5 (range 34-72 years); 13 methylated MGMT, 2 unmethylated (3 unknown); 2 mutated IDH1, 10 wildtype (6 unknown); 16 maximum surgical resection; 17 chemoradiation and adjuvant chemotherapy; 17 received radiation dose of 60Gy in 30#, 1 received 40Gy in 15#; 11 had disease progression requiring further treatment; 5 had no progression, 2 progressed but did not have further treatment. CONCLUSION In Stupp data a 2 year survival of 26.5% was reached. In our real world cohort, a 2 year survival of 21.4% is satisfactory. MGMT methylation was common, but not exclusively the case. Only 2 were IDH1 mutated, possibly reflecting the frequency of occurrence in the GBM population, but demonstrating that it is not a prerequisite for improved survival. Younger age, and maximal surgical resection followed by chemoradiation and adjuvant chemotherapy are associated with improved prognosis. Recognising our dataset is small, we recommend further studies using a larger cohort to improve understanding of better outcomes in this patient group.
Lynch/Turcot Syndrome and Sporadic Mismatch Repair Deficient High-Grade Gliomas – A Case Series
Authors: Mayen Briggs, Jonathan Bruty, Dominic O’Donovan, Hongxiang Liu, Marc Tischkowitz, Patrick Tarpey, Ekkehard Hewer, Olivier Giger
Journal: Neuro-Oncology (2022)

Abstract AIMS The DNA mismatch repair (MMR) system is critical for genomic stability correcting errors generated during DNA replication with germline pathogenic variants (PVs) causing Lynch syndrome. Although acquired MMR deficiency is associated with temozolomide resistance, the incidence in treatment naïve tumours is unknown and not routinely screened for. Here we present three MMR deficient gliomas and describe their comprehensive molecular profile. METHOD Thirteen gliomas; 9/34 that had undergone sequencing of 50 cancer-associated genes and found to have frameshift/multiple point PVs, indicative of defective MMR, and four MSI-high tumours, identified following microsatellite analysis for 1p/19q co-deletion as part of routine care, were selected for analysis. MMR expression was then assessed by immunohistochemistry. Seven tumours showed loss of one or more MMR proteins and were molecularly characterised using PCR-based Promega MSI analysis and NGS-based Illumina TruSight500 panel. RESULTS Pathogenic variants in MMR genes and hypermutated phenotypes (TMB &amp;gt; 10mutations/Mb) were identified in three cases. One individual harboured an additional POLE PV resulting in an ultra-hypermutated phenotype (&amp;gt;100mutations/Mb). Two MMR PVs were germline, leading to a new diagnosis of Lynch syndrome. Only one of three tumours was found to be MSI-high using the Promega MSI analysis whilst all three were identified as MSI-high using TruSight500 MSI calling algorithms. CONCLUSION We describe the comprehensive molecular profile of seven treatment naïve gliomas, three being MMR deficient. We show TruSight500 to be more sensitive and reliable for detecting MSI compared to Promega. Given the implications, this additional analysis should be considered as part of the molecular report on all gliomas.
Systemic Inflammation Is Implicated in De Novo Seizures Following Meningioma Resection
Authors: Ali Bakhsh, Conor Gillespie, Siddhant Kumar, George Richardson, Arish Mustafa, Nasir Mirza, Michael Jenkinson
Journal: Neuro-Oncology (2022)

Abstract AIMS To investigate the association between perioperative peripheral blood inflammatory markers and seizures in patients who have undergone meningioma resection. METHOD A single neurosurgery tertiary centre blood bank database was screened to extract pre-operative and post-operative white cell count (WCC), neutrophils, lymphocytes, monocytes, platelets and neutrophil-lymphocyte ratio (NLR) and derived NLR (dNLR). All patients who underwent resection of meningioma from 2012 to 2020 were eligible. Patients were excluded if they had an inflammatory condition, peri-operative infection, medical illness or operative complication. RESULTS 30 patients suffered pre-operative seizures only, 16 experienced de novo post-operative seizures within 1 year and 42 patients did not experience seizures throughout their treatment timeline. In those who had never had a seizure, there was a significant increase in WCC post-operatively (15.2 vs. 10.6 × 109/L (95% CI 2.1-8.2), p=0.02). Patients who suffered de novo seizures had a significantly higher post-operative day 1 to 4 WCC than those with no seizures (21.1 vs. 14.8 × 109/L (2.1-12.6), p=0.48). However, this difference of WCC was poorly predictive of de novo seizures at one year (AUC 0.61). There was no difference in pre-operative inflammatory markers between pre-operative seizure patients, de novo seizure or never seizure patients. CONCLUSION There is a significantly higher post-operative systemic inflammatory response in patients who suffered de novoseizures after meningioma resection. Peripheral blood markers have the potential to predict seizures in patients with meningioma.